The following processes are known as a process for producing an optically active 1-substituted 2-methylpyrrolidine.    (1) A process for producing (R)-1-benzyloxycarbonyl-2-methylpyrrolidine including converting a hydroxyl group of L-prolinol derived from L-proline to a chloro group with thionyl chloride, protecting a nitrogen atom with a benzyloxycarbonyl group, and radically reducing the product with tributyltin hydride (Non-Patent Document 1).    (2) A process of optically resolving racemic 2-methylpyrrolidine with tartaric acid (Non-Patent Document 2).
However, process (1) includes many steps and uses a highly toxic tin compound. In process (2), crystallization must be repeated a plurality of times, and thus the operation is complex. Thus, any of these processes is not an industrially advantageous process.
If an optically active 1-substituted 2-methylpyrrolidine is derived using an optically active 1,4-pentanediol as a starting material, the above problem would be solved to efficiently produce an optically active 1-substituted 2-methylpyrrolidine. However, any known process for producing the optically active 1,4-pentanediol is not an industrially advantageous process.
For example, the following processes are reported as a process for producing an optically active 1,4-pentanediol.    (3) A process for producing (S)-1,4-pentanediol including coupling an enolate prepared from 2,4,4-trimethyl-2-oxazoline and n-butyllithium and (S)-epichlorohydrin, hydrolyzing the product with hydrochloric acid, and reducing the product with lithium aluminum hydride (Non-Patent Document 3).    (4) A process for producing (S)-1,4-pentanediol including treating D-glutamic acid with nitrous acid to produce γ-butyrolactone-4-carboxylic acid, reducing the carboxylic acid with borane-dimethyl sulfide complex to produce an alcohol, tosylating the hydroxyl group, and reducing the product with lithium aluminum hydride (Non-Patent Document 4).    (5) A process for producing (S)-1,4-pentanediol including reducing a carbonyl group of an ester of levulinic acid (ester of 4-oxopentanoic acid) with baker's yeast, and reducing the product with lithium aluminum hydride (Non-Patent Document 5).    (6) A process for producing (R)-1,4-pentanediol including protecting a hydroxyl group at the 1-position of racemic 1,4-pentanediol with a trityl group, asymmetrically acylating the product with a lipase, separating an ester from the resulting mixture of the ester and an alcohol, and deprotecting with p-toluenesulfonic acid (Non-Patent Document 6).
However, processes (3) and (4) include many steps and require using many expensive reagents. In process (5), the yield of the reductive reaction by the microorganism is low, 60% at the maximum. Furthermore, process (6) is a racemic resolution and thus inefficient.
[Non-Patent Document 1] J. Org. Chem., 1989, Vol. 54, pp. 209-216
[Non-Patent Document 2] Acta. Pharm. Suec., 1978, Vol. 15, pp. 255-263
[Non-Patent Document 3] J. Chem. Soc., Chem. Commun., 1994, pp. 483-484
[Non-Patent Document 4] J. Med. Chem., 1982, Vol. 25, pp. 943-946
[Non-Patent Document 5] Synthetic Communications, 1990, Vol. 20, pp. 999-1010
[Non-Patent Document 6] Bioorganic & Medicinal Chemistry Letters, 1996, Vol. 6, pp. 71-76